Drug Treatments for Kidney Cancer

Your drug treatments for kidney cancer will be based on the stage and grade of your cancer and your general health.

Staging is used to describe the size of your cancer and how far it has spread. Your medical team will also grade your kidney cancer to indicate how quickly or slowly a cancer is likely to grow and spread:

• Stage 1– the cancer is confined to the kidney and is less than 7cm in size
• Stage 2– the cancer is bigger than 7cm but still confined to the kidney
• Stage 3– the cancer has started to spread outside the kidney to the adrenal gland or a major vein nearby. The cancer may have spread to no more than one nearby lymph node.
• Stage 4– the cancer has spread to nearby tissues or organs and more than one nearby lymph node contains cancer cells OR the cancer has spread to other parts of the body further away.

Cancers are graded as; low, intermediate or high grade. This grading indicates how quickly the cancer is likely to grow and spread. Low-grade cancers grow slowly, while high-grade cancers are more aggressive and grow quicker.

Your doctors will advise you of the best  intervention for your stage and grade of cancer this may be surgery or drug treatment if your cancer has spread.

It is important you feel you have been given enough information to make a decision with your medical team about how you will proceed with treatment for your kidney cancer.

Don’t be embarrassed about asking people to explain things again. And remember to ask about any aspects that are worrying you. Sometimes it is helpful to write down the questions you might like to ask. Our kidney cancer information may help and prompt you to the questions that you may have. Surgical Treatments for Kidney Cancer fact sheet and Understanding Kidney Cancer booklet for more information about staging and grading and discussing treatment options.

Biological therapies

Biological therapies are drugs which are used to kill cancer cells or stop them from growing. Biological therapies are used to try to shrink or control advanced kidney cancer and help people to live longer. You may be given biological therapies for kidney cancer that has already spread or is at high-risk of coming back after surgery.

Some people with advanced kidney cancer respond very well to biological therapies, and the treatment can control their cancer for a number of months or even years. There is a great deal of research going on to try to find out why certain patients do so well, and which is the best combination of drugs to give to patients with advanced kidney cancer. You can get more information about clinical trials from here or download our Clinical Trials fact sheet from our library.

Several different types of biological therapy are used for the treatment of advanced kidney cancer, including immunotherapy ( including monoclonal antibodies and targeted therapies). Combinations of immunotherapy  and targeted therapy are approved in Europe and the US.

Targeted Therapies

Drugs such as sunitinib (Sutent®), pazopanib (Votrient®), axitinib (Inlyta®), tivozanib (Fotivda®), and Cabozantinib (Cabometyx®) are  Tyrosine Kinase Inhibitors (TKIs). These drugs block the effects of a protein called tyrosine kinase, which is involved in new blood vessel growth, essential for cancer cells to divide and grow. These treatments starve the tumour by stopping the development of a new blood supply (angiogenesis). These types of medications are called anti-angiogenic agents. Tyrosine kinase inhibitors also interfere with the growth of cancer cells by blocking the signals within the cancer cells that tell them to grow and divide, causing the cancer cells to die .Tyrosine kinase inhibitors come as tablets or capsules taken orally.

Sunitinib comes as a capsule, which is taken once a day for four weeks followed by a two-week break. It may also been taken on schedule of two weeks on and one week off if the standard schedule is not tolerated.

Pazopanib comes in a tablet form and is taken once a day in continuous cycles of six weeks. Axitinib is a tablet and is taken twice a day, ideally 12 hours apart, this treatment is continuous. Tivozanib is an oral tablet taken daily, 3 weeks on and 1 week off.

Cabozantinib is an oral tablet taken daily.

All the treatments may come as several tablets or capsules to make up the dose you are required

to take. TKIs are taken until they are no longer effective, or side effects are unacceptable.

Another group of protein kinase inhibitors, called mTOR inhibitors, everolimus (Afinitor®), this acts in a similar manner to TKIs by interfering with the signalling pathway that controls tumour cell growth and angiogenesis. Everolimus is a tablet that is taken once daily. MTOR inhibitors are treatments for advanced kidney cancer that has come back during or after treatment. Side-effects to mTOR inhibitors are similar to those for TKIs.

A TKI called lenvatanib can be taken with in combination with everolimus when kidney cancer has come back after or during treatment. Lenvatinib is also a tablet and is taken daily.

Potential side-effects to targeted therapies

• Tiredness
• Diarrhoea
• Nausea and vomiting
• Skin and hair discolouration/changes
• Red and blistered hands and feet (palmar-plantar erythrodysaesthesia, PPE)
• Sore mouth
• Raised blood pressure
• Thyroid problems
• Blood problems
• Loss of taste and appetite
• Infection and high temperature

It is important whilst on one of the above medications to monitor your temperature every day and ring the hospitals dedicated hotline it is above 38 degrees Celsius or below 35 degrees Celsius. This might indicate you have an infection and you will need antibiotics as soon as possible.

Many of these side-effects can be controlled with medication and they do not affect everyone. You may only have one or two side-effects. A side effect may get worse through your course of treatment, or more side-effects may develop as the course goes on. It is also important keep a record of the side effects, you have and report these to your medical team

Your clinical nurse specialist (specialist nurse) or doctor should give you a contact number for you to ring if you are worried about side-effects or have any questions. You need to tell your specialist nurse or doctor about your side-effects so they can help you manage them. You also need to tell your doctor about any other medicines you are taking, including vitamins, herbal supplements, and other over-the-counter remedies.

Immunotherapy

The immunotherapy interleukin-2 used to be the main treatments for advanced kidney cancer. This approach stimulates the body’s own immune system to attack the cancer cells. It uses man-made copies of substances found naturally in the body. However, it’s use has been superseded by targeted therapies and monoclonal antibodies , which are more effective at controlling the cancer and have less severe side-effects. As a result, the use of immunotherapy for advanced kidney cancer has declined in recent years. However, a small minority of patients (about 5 per cent), who are otherwise healthy and well enough to withstand the severe side-effects, have a long-term durable response to high doses of interleukin-2. Interleukin-2 therefore still has a place in the treatment of a small percentage of patients where it offers the hope of durable remission. This is available at the Christie in Manchester by referral.

Newer specific immunotherapies (monoclonal antibodies) are now available with combinations of specific immunotherapies with targeted therapies going through the approval process.

Nivolumab (Opdivo®) is an anti-PD-1 (programmed death-1) monoclonal antibody which acts by blocking the receptor PD-1 on T-cells (part of the immune system), which reinvigorates the T-cells and allows them to attack the cancer cells. T-cells are often inactivated by a substance that cancer cells produce, which activates the PD-1 receptor on T-cells. Activating the PD-1 receptor causes the T-cell to become inactive so it does not do its job and attack cancer cells. Nivolumab acts as an immunomodulator and stops the PD-1 receptor from being activated which in turn boosts the body’s own ability to attack cancer cells.

The PD-1 blockade is thought to specifically reinvigorate immune cells that are able to target cancer. It does not generally activate the entire immune system, and this could help to reduce the side effects of the drug. Nivolumab is generally well tolerated but can cause inflammatory conditions in varying organs of the body.

Nivolumab is currently approved in the UK for use as a second line treatment of metastatic kidney cancer. This means they have had initial treatment with a targeted treatment  first but needed more treatment.

Nivolumab and Ipilimumab ( Opdivo®and Yervoy ®) is a combination immunotherapy treatment. Ipilimumab targets a different protein CTLA-4. In this combination, Ipilimumab works together with nivolumab to help shrink the tumour. The side effects of the combination are similar to nivolumab alone. This is approved for first line treatment in intermediate and poor risk patients.

Currently new combination treatments are being reviewed in the UK. These treatments use immunotherapy and tyrosine kinase inhibitors in combination to treat advanced kidney cancer.

Each of the treatments for kidney cancer are prescribed in accordance with the governing body in the specific country they may be NICE, SMC or AWTCC. They recommend which treatments can be given for each subtype of renal cancer and in what order they should be given.

In the UK, sunitinib, pazopanib and tivozanib are commonly used as first-line treatment for advanced kidney cancer that had been categorised as  favourable risk ( IMDC) . Those with intermediate or poor risk may be offered nivolumab and ipilimumab or carbozantanib.

Avelumab + Axitinib

Avelumab is a type of cancer treatment known as immunotherapy. This type of targeted treatment works with your immune system, increasing its natural ability to identify and attack cancer cells. It works by attaching to a specific target in on the cancer cells called programmed-death ligand 1 (PD-L1).

PD-L1 is found on the surface of cancer cells and helps protect cancer cells from the immune system (the body’s natural defence). Avelumab binds to PD-L1, and blocks this protective effect, allowing the immune system to attack the tumour cells.

Axitinib is a type of cancer treatment known as a tyrosine kinase inhibitor (TKI). This type of targeted treatment works by blocking the action of certain proteins called tyrosine kinases. Tyrosine kinases are found on the surface of cancer cells and stimulate the growth of blood vessels from existing vessels, which allows cancer cells of the tumour to grow and spread. Axitinib binds to tyrosine kinases and blocks the formation of new blood vessels, preventing tumour growth and spread.

The rationale for combining avelumab and axitinib is that their different mechanisms of action may complement each other in the treatment of RCC.

The choice of a second line treatment, given when the first treatment ceased to be effective or can’t be tolerated is dependent what has initially been given. If sunitinib or pazopanib was used first, then immunotherapy agent nivolumab can be offered on its own. If immunotherapy has been given in a first line a TKI  will be given such as axitinib , cabozantanib or the combination of lenvatinib and evorolimus. Each case will be different and will be dependant on the person.

Drug treatments available on the NHS:

• Interleukin-2 or Aldesleukin (Proleukin®) – only at The Christie, Manchester (patients can be referred from anywhere in the UK)
• Sunitinib (Sutent®)
• Pazopanib (Votrient®)
• Axitinib (Inlyta®)
• Cabozantanib ((Cabometyx®)­
• Nivolumab (Opdivo®)
• Tivozanib (Fotivda®),
• Lenvatinib with Everolimus (Afinitor®)
• Avelumab and Axitinib
• Nivolumab with Ipilimumab (Opdivo®and Yervoy ®)

Drugs currently under review:

• Pembrolizumab and Axitinib
• Nivolumab and Cabozantinib